NOTE: The information contained in this edition of MPE-L is designed to help of owners of those pet rats (Rattus norvegicus) who are/may be infected with Mycoplasma pulmonis (‘myco’ or MP). Although MP does infect mice, the lungs of mice and rats are different, and certain material may not be applicable.
The information in this issue of MPE-L can be found in the following sources:
1. What is a mycoplasma?
Mycoplasmas are also referred to as PPLO (Pleuropneumonia-like organisms), and are usually classified today as an unusual form of bacteria (or simply as mycoplasmas). In older texts, you may find mycoplasmas categorized as viruses or identified as unknown agents. There are many different mycoplasmas (approx. 95); however, we are interested in one: Mycoplasma pulmonis [MP]. ‘Mycoplasma’ refers to the organism’s genus and ‘pulmonis’ the species. The following list illustrates the pertinent taxonomic hierarchy for Mycoplasma pulmonis:
Class - Mollicutes (Latin - soft skin)
Order - Mycoplasmatales
Family - Mycoplasmataceae
Genus - Mycoplasma
Species - pulmonis
Strain - ? (multiple)
The word ‘mycoplasma’ as we commonly use it actually refers to all the organisms in the class Mollicutes. Mycoplasmas are unique because they do not possess cell walls, unlike most bacteria. The importance of this lack of cell walls will become apparent in later discussions of antibiotic therapy. "Mycoplasmas are very fragile outside the host; the organisms are highly susceptible to heat, detergents, disinfectants, and antimicrobial drugs that inhibit transcription, translation, or the DNA gyrase enzyme" (Gyles and Thoen, 298). Gyrase aside, this means that washing your hands thoroughly with hot water and soap will kill MP. Also, there is very little evidence that transmission of MP actually occurs from contaminated clothing or equipment, most likely due to the delicate structure of the MP organism.
2. Can I catch MP from my rat?
No. Mycoplasmas in general tend to be host specific, and MP is not a known human pathogen. Your system cannot become infected with MP; however, your skin, clothes, and equipment could technically carry the infectious fluids of a diseased animal, although not for long. Mycoplasmas live on mucosal surfaces: genital tracts, respiratory passages, and lungs. Therefore any contact with infected mucous membranes or mucosal fluids (commonly known as ‘snot’) may infect healthy rats. One common way MP spreads through a colony is aerosolized respiratory secretions from coughing or sneezing rats over short distances. Sexual contact, contact with an infected doe’s birth canal, and mutual grooming practices are other avenues of transmission. MP is an extremely contagious, but manageable pathogen.
3. Can my rat ‘catch’ MP from me?
Your ability to transmit MP to your pet rat is stymied on several fronts. First, as a human being, you are unable to become infected with MP and therefore expose your rat to infected body fluids (although MP can be temporarily carried inside human nasal passages). Second, MP is very fragile, and rarely remains viable for long on clothing, exposed skin, or equipment.
Mycoplasmas are delicate and tend to have slow rates of growth. Also, virulence varies widely in different strains of MP. "The dose of M. pulmonis required to induce gross pneumonic lesions in 50% of challenged mice can vary from 103 colony forming units (CFU) to >107 " (Gyles and Thoen, 303). It is important to note that once MP is allowed to take root in a rat’s system, the organism may be nearly impossible to eradicate. Strains of MP mimic certain rat antigens with variable surface proteins, effectively fooling the rat’s immune system into ignoring the invading organism. This biological mimicry, in conjunction with multiple other factors, explains why rats have such diverse reactions to MP exposure and subsequent infection.
Correct and prompt antibiotic therapy is essential whenever MP is suspected. However, individuals not actively involved in the field of microbiology have a tendency to attribute every chronic illness to mycoplasmas, (as the number of human malpractice cases linked to mycoplasma misdiagnosis might indicate) (IS Labs; inter alia). Only certain antibiotics have an effect on MP, and that class of antibiotics may be inappropriate to combat other infections. While MP is a common rat disease, it certainly is not the only pathogen capable of striking your animal.
4. Why can’t we just breed a MP resistant rat?
We already have! (Before you get excited, it’s the Fisher 344, a particular type of laboratory rat.) For pet rats, the story is different, and requires some details about the immune response to MP to understand.
Most animals possess two types of internal defense responses: nonspecific, which does not depend on the antigen, and specific, which are tailored to a particular type of antigen. (An antigen is any substance capable of triggering an immune response.) In general, the specific defense response is the more effective of the two.
Immune responses depend upon the ability of an organism to distinguish between matter which is part of the organism (‘self’) and foreign matter (‘nonself’). To make this distinction, organisms rely on surface macromolecules, which are proteins or large carbohydrates that are can be used to distinguish between different species, or individuals of the same species. It is the presence of these foreign macromolecules that stimulates the immune response, and the recognition of the specific foreign antigens that makes the specific immune response possible.
Typically, a bacterial invasion triggers a response of the immune system. Ideally: nonspecific defense mechanisms destroy pathogens and prevent the spread of infection for the few to several days required to get the specific defense mechanisms going. If the bacterial invasion is still present at that point, it is destroyed by the extremely effective specific immune response. Memory cells remain after the invasion is destroyed so that a secondary invasion can be met much more quickly with a specific immune response. In the real world, bacteria have various characteristics which impede the effectiveness of one or more parts of this system in different ways; MP is no exception.
Mycoplasmas are bacteria, with an enclosing lipid and protein membrane, but no cell-wall outside this membrane. (Aside: this is one of the primary reasons that a careful selection of antibiotic is important. Many, if not most, antibiotics affect either cell-wall synthesis or cell-wall integrity. These antibiotics are obviously not well-suited to treating MP.) With some exceptions Mycoplasmas are host-specific. This specificity may be related to the availability of specific receptors in the host organism, or the ability of the host organism to identify the parasite as ‘nonself’.
MP causes a disease called murine mycoplasmosis at the site of infection. The disease murine mycoplasmosis has a myriad of symptoms including chronic respiratory disease, pneumonia, infertility, and abortion/reabsorbtion, depending on the site. Rats carrying MP in their lungs are often also infected by other bacteria, theoretically because the integrity of their lung walls has been compromised by the invasion of the mycoplasmas. MP, like most Mycoplasmas, are thought to be solely external parasites, but evidence suggests that it is difficult to kill the bacterium without killing the host cell.
Susceptibility to MP colonization can be significantly affected by environmental stress factors and pollutants; of specific interest to pet rat owners is the increase in susceptibility conferred by exposure to ammonia [NH3]. Rat fecal material and especially urine release ammonia into the air, which in turn irritates the mucosal epithelial layer (the mucous membrane). There are also genetic differences in susceptibility; for example, Fisher 344 rats do not seem to develop pneumonia when exposed to MP, while other types of laboratory rats do. Even among different strains of the same species, virulence varies over a wide range. As if this was not enough variation, Mycoplasma diseases are examples of multifactorial diseases, meaning that many factors influence the final outcome of infection.
The underlying cause of many of the aforementioned phenomena, and the underlying reason for the various immune response to MP (or lack thereof) is that it has a "highly variable surface-expressed protein." This means that MP’s antigenic makeup varies (the surface macromolecules required for the host organism to identify the bacterium are not constant), and this allows MP to avoid eradication by the specific immunological response normally tailored to destroy a particular pathogen. There are several specific resulting disturbances of the immune system; one example is the ‘biological mimicry’ mentioned above, in which the host organism is unable to recognize the bacterium as nonself, and therefore does not initiate a specific immune response. Another manifestation is that MP is mitogenic for lympocytic T and B cells. This results in the production both of irrelevant antibodies, and what is worse, antiimmune antibodies, which actually attack the host organism. This mitogenic susceptibility is at the root of the Fisher 344 rats ‘immunity’ to MP: the Fisher 344 rats seem to have reduced mitogenic susceptibility, not just to MP but to all mitogens. It is also responsible for the persistence of the bacterial invasion in the host organism (to the extent that the changing antigenic makeup enables MP to escape ‘immune surveillance’, the host organism’s attempts to identify foreign matter.) For example, recovery from typhoid confers a lifetime immunity upon a person, owing to the memory cells created by the specific immune response. With no specific antigenic pattern to match, there is no immunity to MP created by a successful recovery.
So what’s the answer? It is not possible to breed a rat which will be ‘immune’ to MP by virtue of a specific immune response, for reasons previously discussed. It is possible, and desirable, to breed rats with ‘stronger’ immune systems (for example, the reduced mitogenic susceptibility of the Fisher 344 rat) or other biological characteristics which assist the rat in dealing with the effects of myco. This would seem to be a more noble goal than intentionally overlooking the health of rats while breeding for ‘desirable’ external biological characteristics - and in the long term, more beneficial to the rat breeding industry. (Some breeders are already attempting to do this, including one of our own ratlisters - AristoRats, of Northern Illinois.) However, the degree of variance of the manner in which murine mycoplasmosis runs its course would make it very difficult, if not impossible, to assess the effectiveness of these attempts. It would be incorrect for promising short-term results to be interpreted as ‘evidence’ of success, for the number of factors already demonstrated to affect the infection outcome would make the environment impossible to control. Over an extended time period, however, such efforts will make a difference.
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